Lin Ming-Tseh, Storer Barry, Martin Paul J, Tseng Li-Hui, Grogan Bryan, Chen Pei-Jer, Zhao Lue P, Hansen John A
Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D2-100, PO Box 19024, Seattle, WA 98109-1024, USA.
Blood. 2005 Dec 1;106(12):3995-4001. doi: 10.1182/blood-2004-11-4338. Epub 2005 Aug 18.
We have previously shown that the interleukin 10 (IL-10)/-592A allele of the recipient is associated with less severe acute graft-versus-host disease (GVHD) and a lower risk of nonrelapse mortality after hematopoietic cell transplantation (HCT) from an HLA-identical sibling. In the present study, we examined variation in the IL-10 receptor beta gene as a further test of the hypothesis that the IL-10 pathway regulates the risk of acute GVHD. A single nucleotide polymorphism (A/G) at cDNA position 238 of the IL-10 receptor beta gene (IL10RB/c238) was genotyped in 953 HC transplant recipients and their HLA-identical sibling donors. IL-10/-592 and IL10RB/c238 genotypes were tested for association with GVHD by multivariable analysis. The IL-10/-592A allele of the recipient and IL10RB/c238G allele of the donor were significantly associated with a lower risk of grades III-IV acute GVHD (trend P < .001 and P = .02, respectively). The donor IL10RB/c238G allele provided protection among patients with the IL-10/-592 A/C or A/A genotypes but not among patients with the high-risk IL-10/-592 C/C genotype. These data suggest an interaction of the patient IL-10/-592 and donor IL10RB/c238 genotypes on risk of GVHD, further supporting the hypothesis that the IL-10 pathway plays an important role in controlling the severity of acute GVHD.
我们之前已经表明，受体的白细胞介素10（IL-10）/-592A等位基因与较轻的急性移植物抗宿主病（GVHD）以及来自HLA相同同胞的造血细胞移植（HCT）后较低的非复发死亡率风险相关。在本研究中，我们检测了IL-10受体β基因的变异，作为对IL-10途径调节急性GVHD风险这一假说的进一步验证。在953例造血细胞移植受者及其HLA相同的同胞供者中，对IL-10受体β基因（IL10RB/c238）cDNA位置238处的单核苷酸多态性（A/G）进行了基因分型。通过多变量分析检测IL-10/-592和IL10RB/c238基因型与GVHD的相关性。受体的IL-10/-592A等位基因和供者的IL10RB/c238G等位基因与III-IV级急性GVHD风险较低显著相关（趋势P分别<0.001和P = 0.02）。供者IL10RB/c238G等位基因在具有IL-10/-592 A/C或A/A基因型的患者中提供保护作用，但在具有高风险IL-10/-592 C/C基因型的患者中则不然。这些数据表明患者的IL-10/-592和供者的IL10RB/c238基因型在GVHD风险上存在相互作用，进一步支持了IL-10途径在控制急性GVHD严重程度中起重要作用的假说。
